Journal
ONCOGENE
Volume 37, Issue 3, Pages 313-322Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2017.330
Keywords
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Funding
- Movember [NKI01]
- KWF Dutch Cancer Society/Alpe d'HuZes Bas Mulder Award [NKI 2014-6711]
- Netherlands Organisation for Scientific Research (NWO) [016.156.401]
- NWO as part of the National Roadmap Large-scale Research Facilities of the Netherlands [184.032.201]
- VIDI grant [723.012.102]
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Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13. In summary, by combining proteomic and genomic approaches we reveal subclasses of AR transcriptional complexes, differentiating normal AR behavior from the oncogenic state. In this process, the expression of AR interactors has key roles by reprogramming the AR cistrome and interactome in a genomic location-specific manner.
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